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When high cholesterol is a family affair

Most of us with high cholesterol have the garden-variety type brought on by eating too much cholesterol and saturated fat and too few fruits, vegetables, and whole grains. More than half a million Americans, though, have a more dangerous type. It stems from an inherited error that can send harmful low-density lipoprotein (LDL) cholesterol into the stratosphere. This often undetected condition, called familial hypercholesterolemia, can cause an early heart attack, stroke, or premature death. Since the name of the disease is a mouthful, we'll refer to it as FH.

Genetic roots

The cholesterol in your bloodstream comes from two sources. Food provides some of it; your body makes the rest. Because cholesterol is a waxy substance, it can't dissolve in the watery bloodstream. To get around this problem, the body packages it with proteins and other fats into a variety of particles that mix easily with blood. One important cholesterol carrier is LDL.

When a cell needs cholesterol, proteins on its surface called LDL receptors pull in LDL from the bloodstream. If these receptors don't work properly, LDL lingers longer in the bloodstream. This allows more LDL to get into artery walls and other undesirable places.

A single main gene codes for the LDL receptor protein. People with FH have a malfunctioning gene. Those who inherit just one copy of the bad gene (from one parent) have what's called heterozygous FH. Although half their LDL receptors don't work, the other half do. Individuals who get a malfunctioning gene from both parents don't have any functioning LDL receptors. This is called homozygous FH.

Facts about FH

One person in 500 has it.

Signs of the disease include very high LDL and possibly cholesterol deposits in the tendons or skin.

Only about 10% to 20% of people with FH know they have it.

If untreated, 85% of men and 50% of women with FH will have a heart attack, stroke, or cardiac arrest before age 65.

Individuals with FH will pass it on to about half of their children.

Detecting FH

Many people with FH don't know they have it. Instead, they (and their doctors) often think they just have tough-to-treat high cholesterol. Your doctor might want to work you up for FH if you have one or more of the following:

total cholesterol above 300 mg/dL (250 mg/dL in children)

LDL above 200 mg/dL (150 mg/dL in children)

early heart disease or very high cholesterol in your immediate family (a father or brother under age 55, a mother or sister under age 65)

cholesterol deposits in the Achilles or other tendons.

Treating FH

Cholesterol control is the centerpiece of coping with FH. It starts with diet, exercise, and lifestyle changes, then extends to cholesterol-reducing drugs.

Cutting back on foods rich in cholesterol and saturated fat, such as red meat and full-fat dairy products, helps lower LDL. So does eating fish, whole grains, vegetables, and vegetable oils — all good sources of unsaturated fats. Controlling blood pressure, exercising, and not smoking are also essential for protecting the heart and blood vessels.

A cholesterol-lowering statin is the usual starting point for drug therapy. Adding a drug such as ezetimibe (Zetia), niacin, or colesevelam (WelChol) can cut LDL even further. The goal is an LDL under 100 mg/dL or, if that's not possible, at least a 50% reduction.

People with homozygous FH don't benefit much from statins and other drugs, which work in part by increasing the body's production of LDL receptors. They periodically need LDL apheresis, a dialysis-like procedure to filter LDL out of the bloodstream.

Alerting others

If you have FH, it's important that your family members be tested for it, too. Children of a parent with heterozygous FH have a 50% chance of inheriting the defective gene; it's 100% if a parent has homozygous FH.

Early testing, followed by aggressive cholesterol control, can delay or prevent the early heart attacks and death that often accompany FH.

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